The proposed project's broad objective is to identify components involved in the regulatory crosstalk between metabolism and immunity, namely cytokine signals that attenuate inflammation associated with nutritional imbalance. Published studies have demonstrated a role for alternative activation of adipose tissue macrophages in metabolism, as a deletion of these cells leads to diet-induced obesity and insulin resistance. The closely related cytokines Interleukin (IL)-4 and IL-13 are known inducers of macrophage alternative activation;therefore, this suggests that IL-4/IL-13 may influence metabolism. We hypothesize that immune cells in adipose tissue provide IL-4/IL-13 to induce macrophage alternative activation, and therefore have physiological implications in energy homeostasis in peripheral tissues. In pursuit of this hypothesis, our specific aims are to: 1) demonstrate the presence of alternatively activated macrophages in vivo in adipose tissue;2) identify cells in adipose tissue producing IL-4 and IL-13;and 3) investigate the metabolic consequences of IL-4/IL-13-deficiency. By utilizing reporter mouse models developed in our laboratory, we are equipped to directly analyze adipose tissue by flow cytometry and histology for IL-4/IL-13- producing cells and alternatively activated macrophages. Identifying a role for these cytokines will provide potential targets to treat diseases of nutritional imbalance such as obesity and insulin resistance. PUBLIC HEALTH RELEVANCE: The goal of our proposed project is to identify cells in fat tissue that supply signals that potentially help control weight gain and blood glucose levels in the body. We believe that our proposed project is highly relevant to public health and biomedical research, as it may help elucidate novel ways to design therapies in order to address the growing epidemic of obesity and its associated complications such as Type 2 diabetes mellitus.